Credit: David Parkins

图片来源：大卫·帕金斯

In the United States, healthy people are routinely screened for signs of a handful of cancers — women entering middle age should schedule a routine mammogram to check for breast cancer, for example.

在美国，健康人会定期接受几种癌症的筛查——例如，步入中年的女性应安排常规乳腺X光检查以排查乳腺癌。

Unfortunately, this kind of early-detection programme is not the norm for all cancers; most malignancies are spotted only at more advanced stages, when people already have symptoms and treatments are much less effective. “All those cancers that we don’t screen for amount to somewhere around 70% of all cancer-related deaths,” says Nima Nabavizadeh, a radiation oncologist at Oregon Health Sciences University in Portland..

不幸的是，这种早期检测项目并不是所有癌症的常态；大多数恶性肿瘤只有在更晚期阶段，当人们已经出现症状且治疗效果差得多时才会被发现。波特兰俄勒冈健康科学大学的放射肿瘤学家尼玛·纳巴维扎德说：“我们没有进行筛查的那些癌症约占所有癌症相关死亡的70%。”

Devising ever-more swabs and scans to detect each and every cancer out there “is just not scalable”, Nabavizadeh says — achieving broad access and adherence to the four cancer screening tests currently recommended in the United States has already proved to be challenging. But what if you could get all the answers from a vial of blood? Therein lies the appeal of multi-cancer early detection (MCED) tests, which scan body fluids for snippets of DNA, proteins and other molecular traces that might reveal a hidden tumour.

纳巴维扎德说，设计越来越多的拭子和扫描来检测每一种癌症“根本不可行”——在美国，实现对目前推荐的四种癌症筛查测试的广泛获取和依从性已经证明是具有挑战性的。但是，如果你能从一管血液中得到所有答案呢？这就是多癌早期检测（MCED）测试的吸引力所在，这些测试通过扫描体液中的DNA片段、蛋白质和其他可能揭示隐藏肿瘤的分子痕迹来进行检测。

Several such tests are in development, and a few have even been assessed clinically..

几个这样的测试正在开发中，甚至有一些已经进行了临床评估。

The results from some of these early studies are promising. “I know cancer patients who now have an early-stage cancer diagnosis that they wouldn’t have known about otherwise,” says Nabavizadeh, who has been involved with studies of an MCED test called Galleri, developed by a company called Grail in Menlo Park, California.

一些早期研究的结果令人鼓舞。 “我知道一些癌症患者，现在他们得到了早期癌症诊断，否则他们不会知道，”纳巴维扎德说，他参与了一项名为Galleri的MCED测试的研究，该测试由加利福尼亚州门洛帕克的一家名为Grail的公司开发。

A few of these tests — including Galleri — are making their way to the market. However, no MCED has yet received formal regulatory approval, and none is covered by US health insurance..

其中一些测试（包括 Galleri）正在进入市场。然而，目前尚无 MCED 获得正式的监管批准，也没有任何测试被美国健康保险覆盖。

Many uncertainties still surround MCED tests. These include determining which cancers they can detect reliably, how clinicians should follow up on positive tests, and whether the use of these tests can meaningfully reduce the number of cancer deaths. “Screening interventions that are done on very broad swaths of the population — most of whom will not benefit — should be very well characterized,” says Hilary Robbins, an epidemiologist at the World Health Organization’s International Agency for Research on Cancer in Lyon, France.

多癌早期检测（MCED）测试仍存在许多不确定性。这些问题包括确定它们能可靠检测哪些癌症、临床医生应如何跟进阳性测试结果，以及这些测试的使用是否能够有效减少癌症死亡人数。世界卫生组织下属国际癌症研究机构（位于法国里昂）的流行病学家希拉里·罗宾斯表示：“针对广大人群进行的筛查干预措施——其中大多数人并不会从中受益——应该得到非常充分的验证。”

“And their benefits should be proven before they’re rolled out.”.

“在推广之前，应该先证明它们的益处。”

Tracking a tumour’s traces

追踪肿瘤的痕迹

The goal of cancer screening is to detect molecular or physiological indicators associated with early-stage malignancy while generating as few false positives as possible. Familiar methods such as mammography for breast tumours are imperfect, but have a track record of reducing the number of cancer deaths..

癌症筛查的目标是检测与早期恶性肿瘤相关的分子或生理指标，同时尽可能减少假阳性。像乳腺肿瘤的乳房X光检查等熟悉的方法并不完美，但有减少癌症死亡人数的记录。

For MCEDs, the challenge is steeper. A test must identify a set of molecular features, or biomarkers, that are associated with a broad spectrum of tumours and that can be measured in an easily obtained specimen such as blood. The most widely employed biomarkers for MCEDs are based on cell-free DNA (cfDNA) that is circulating in the bloodstream.

对于MCEDs，挑战更为严峻。检测必须识别一组与广泛肿瘤相关的分子特征或生物标志物，并且这些标志物可以通过容易获取的样本（如血液）进行测量。目前最广泛用于MCEDs的生物标志物是基于在血液中循环的无细胞DNA（cfDNA）。

cfDNA is a natural by-product of cell death, and is already used to look for fetal congenital abnormalities..

cfDNA是细胞死亡的天然副产品，已经被用于寻找胎儿先天性异常。

Genomic fragments are also a known by-product of tumour-cell proliferation. But turning these fragments into a viable indicator for early cancer detection has taken considerable effort, because the small fraction of DNA shed by tumour cells is drowned out by the much larger quantity from normal cells.

基因组片段也是肿瘤细胞增殖的已知副产品。但是，将这些片段转化为早期癌症检测的可行指标需要付出相当大的努力，因为肿瘤细胞释放的DNA小部分被正常细胞释放的更大量的DNA所淹没。

Finding cancer in this way is a “needle in a haystack” problem, says Nickolas Papadopoulos, an oncologist at Johns Hopkins Medicine in Baltimore, Maryland..

通过这种方式发现癌症是一个“大海捞针”的问题，马里兰州巴尔的摩约翰霍普金斯医学中心的肿瘤学家尼克拉斯·帕帕多普洛斯说道。

Rapid improvements in the speed, accuracy and throughput of DNA sequencing, accompanied by falling costs, have made it possible to uncover the signal buried in this noise. In 2014, Papadopoulos was part of a team that demonstrated that they could detect cancer-related cfDNA signatures in people already known to have one of a variety of different cancers.

DNA测序的速度、准确性和通量的快速提升，以及成本的下降，使得从这些噪音中挖掘信号成为可能。2014年，帕帕多普洛斯参与了一个团队，证明了他们可以检测到已知患有各种不同癌症的人体内的癌症相关cfDNA特征。

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. The team subsequently expanded on its work with one of the earliest MCED tests, called CancerSEEK. That system is now being developed commercially under the name Cancerguard by Exact Sciences, based in Madison, Wisconsin.

该团队随后在其最早期的MCED测试之一CancerSEEK的基础上扩展了其工作。该系统现在正由总部位于威斯康星州麦迪逊的Exact Sciences公司以Cancerguard的名称进行商业开发。

Part of Nature Outlook: Medical diagnostics

自然展望的一部分：医学诊断

Other companies are also clinically testing cfDNA-based MCED tests, including Grail, Singlera Genomics in La Jolla, California, and Burning Rock Biotech in Guangzhou, China. Some tests search for mutations or chromosomal structural abnormalities linked to cancer. Others, including Galleri, examine DNA methylation, which exerts a potent regulatory effect on gene expression.

其他公司也在对基于cfDNA的MCED测试进行临床试验，包括Grail、加利福尼亚州拉霍亚的Singlera Genomics以及中国广州的燃石生物技术公司。一些测试寻找与癌症相关的突变或染色体结构异常。其他的测试，包括Galleri，则检查DNA甲基化，这对基因表达有强大的调控作用。

Grail oncologist Eric Klein says the company has developed machine-learning algorithms that can use methylation profiles to reveal not only the presence of cancer but also its tissue of origin, with an accuracy exceeding 90%. Cancerguard also assesses cfDNA methylation, but alongside other protein biomarkers that are known indicators of specific cancers, such as prostate-specific antigen for prostate cancer..

Grail的肿瘤学家埃里克·克莱因表示，该公司已经开发出机器学习算法，可以利用甲基化图谱不仅揭示癌症的存在，还可以确定其组织来源，准确率超过90%。Cancerguard也评估cfDNA甲基化，但同时结合了其他已知的特定癌症蛋白生物标志物，例如前列腺癌的前列腺特异性抗原。

Most MCED tests have been assessed only using samples from people with a known cancer diagnosis — which often means that the tumour is sufficiently developed enough as to cause symptoms. But there have been two prospective studies in which apparently healthy participants were tested and then evaluated more closely to determine whether positive results were accurate.

大多数MCED测试仅使用已知癌症诊断患者的样本进行评估——这通常意味着肿瘤已经发展到足以引起症状的程度。但也有两项前瞻性研究，对看似健康的参与者进行了测试，然后进行了更详细的评估，以确定阳性结果是否准确。

The first, the DETECT-A study, evaluated the CancerSEEK test in more than 10,000 women aged 65—75.

第一项研究，即DETECT-A研究，在10,000多名65至75岁的女性中评估了CancerSEEK测试。

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. Grail’s Pathfinder study of Galleri, by contrast, looked at both men and women over the age of 50, and included more than 6,600 people

相比之下，Grail的Pathfinder研究针对Galleri检测，纳入了50岁以上的男性和女性，且人数超过6600人。

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DETECT-A combined its blood test with whole-body imaging, and achieved a positive predictive value (PPV) of 28%. This means that around 1 in 4 positive tests represented a real cancer diagnosis. Pathfinder relied entirely on blood-based cfDNA testing to make its preliminary diagnostic call, and achieved a PPV of 38% — more than 1 in 3 positive tests were accurate.

DETECT-A 将其血液检测与全身成像结合，达到了 28% 的阳性预测值 (PPV)，这意味着大约每 4 次阳性检测中就有 1 次代表真实的癌症诊断。Pathfinder 完全依靠基于血液的 cfDNA 检测来进行初步诊断判断，并实现了 38% 的 PPV —— 超过三分之一的阳性检测结果是准确的。

These PPVs might seem modest, but given that testing generated a relatively small number of hits overall, this means that few test recipients will experience a false-positive test (see ‘Two major trials of multi-cancer early detection systems have yielded encouraging results’)..

这些PPV看似不高，但由于检测总体上产生的阳性结果数量相对较少，这意味着很少有检测接受者会经历假阳性结果（参见“两项多癌早期检测系统的主要试验取得了令人鼓舞的结果”）。

Two major trials of multi-cancer early detection systems have yielded encouraging results.

两项多癌早期检测系统的主要试验取得了令人鼓舞的结果。

Pathfinder (blood only)

路径寻找器（仅限血液）

DETECT-A (blood and PET-CT*)

DETECT-A（血液和PET-CT*）

Number of participants evaluated

参与评估的人数

6,621 (63.5% female)

6,621（63.5%为女性）

9,911 (100% female)

9,911（100%女性）

Positive signal

积极信号

92 (1.4%)

92（1.4%）

53 (0.5%)

53（0.5%）

Positive predictive value (percentage of positives that are true positive)

阳性预测值（真阳性占阳性的百分比）

38%

38%

28.3%

28.3%

Share of participants who got a false-positive result

得到假阳性结果的参与者比例

0.87%

0.87%

0.36%

0.36%

Negative predictive value (percentage of negatives that are true negative)

阴性预测值（真阴性在所有阴性中的百分比）

98.6%

98.6%

99.1%

99.1%

Diagnosed cancers that were solid tumours versus blood cancers

诊断出的实体肿瘤癌症与血液癌症

53% solid, 47% haematological

53%为实体瘤，47%为血液肿瘤

93% solid, 7% haematological

93%实体，7%血液学

Share of newly diagnosed cancers that were early-stage (stage 1 or 2)

早期诊断癌症（第一或第二阶段）占新诊断癌症的比例

48% (14 out of 29)

48%（29个中的14个）

47% (7 out of 15)

47%（15个中的7个）

*Positron emission tomography–computed tomography

*正电子发射断层扫描-计算机断层扫描

Exact Sciences’ chief medical officer Tomasz Beer says this modest true-positive rate is a feature, not a bug, of current MCED studies. “They’re all aiming for high specificity to limit false positives,” he says. And indeed, both Pathfinder and DETECT-A achieved an overall false-positive rate of roughly 1% across the entire cohort that underwent testing — notably better than what many existing single-cancer screening methods achieve.

Exact Sciences的首席医疗官托马斯·比尔表示，目前的MCED研究中这种较为适中的真阳性率是一项特性，而非缺陷。“他们的目标都是实现高特异性，以减少假阳性，”他说。确实，Pathfinder和DETECT-A在整个接受测试的群体中，总体假阳性率约为1%——明显优于许多现有的单癌筛查方法。

“Currently recommended screening tests pick up 5–10% of people who don’t have cancer,” says Allan Hackshaw, a cancer epidemiologist at University College London. Those people “go through biopsies, all the imaging scans, and it can take one or two months before they find out that they don’t have cancer after all”..

“目前推荐的筛查测试会发现5%-10%的人并没有患癌症，”伦敦大学学院的癌症流行病学家艾伦·哈克肖说。那些人“经历了活检、所有的影像扫描，要花一两个月的时间才能最终确认他们根本没有患癌症”。

It is also important to note that a majority of the tumours picked up by MCEDs would have otherwise gone undetected. Indeed, says Klein, Pathfinder caught twice as many cancers as would have been observed with standard screening procedures.

同样重要的是，大多数被MCED检测到的肿瘤原本可能会被漏检。克莱因表示，Pathfinder 检测出的癌症数量是标准筛查程序所能发现的两倍。

Early enough to matter?

足够早了吗？

These encouraging numbers conceal hidden complexity, however. “It’s not just about the test — it’s about the test combined with the cancer’s amenability to early detection,” explains Ruth Etzioni, a biostatistician at the Fred Hutchinson Cancer Center in Seattle, Washington.

然而，这些令人鼓舞的数字隐藏了复杂性。“这不仅仅是关于测试——而是关于测试与癌症对早期检测的适应性相结合，”华盛顿州西雅图弗雷德·哈钦森癌症中心的生物统计学家露丝·埃齐奥尼解释说。

Although the aim is to catch cancer early, some of the correct diagnoses that the tests yielded were of late-stage disease that had passed unnoticed. In DETECT-A, only 65% of diagnoses represented early-stage disease; in Pathfinder, it was only 48%. Performance also varied across tissues. For example, most of the early-stage cancers detected in Pathfinder were blood malignancies.

尽管目标是尽早发现癌症，但检测结果中的一些正确诊断却是之前未被察觉的晚期疾病。在DETECT-A研究中，只有65%的诊断属于早期疾病；而在Pathfinder研究中，这一比例仅为48%。不同组织的表现也有所不同。例如，Pathfinder研究中检测到的大多数早期癌症是血液恶性肿瘤。

“That’s something to consider because detecting haematological cancers like lymphoma early is not as important as detecting solid tumours early,” says Robbins..

“这是需要考虑的，因为早期检测像淋巴瘤这样的血液癌症并不像早期检测实体肿瘤那么重要，”罗宾斯说。

Making kidney tests work for everyone

让肾功能检测适用于每个人

This inconsistency is partly attributable to the characteristics of cfDNA itself as a biomarker, which shows considerable variability across cancers. Lung, ovarian, liver and gastric tumours shed more cfDNA than do thyroid, breast and prostate cancers, says Beer, and the heavier shedders will be easier to spot.

这种不一致性部分归因于cfDNA作为生物标志物本身的特性，它在不同癌症中表现出相当大的变异性。比尔表示，肺癌、卵巢癌、肝癌和胃癌释放的cfDNA比甲状腺癌、乳腺癌和前列腺癌更多，因此那些释放较多的肿瘤将更容易被检测到。

Very early-stage and premalignant growths also release less cfDNA and are likely to be missed by MCED testing. Hackshaw thinks this could be advantageous, because many such growths never turn into cancer, and a ‘hit’ here could drive more people towards overtreatment of cancers that would not have caused problems if they had gone undetected, which remains a problem for prostate and breast cancer.

非常早期和癌前生长也释放较少的cfDNA，很可能被MCED检测忽略。Hackshaw认为这可能是一个优势，因为许多这样的生长永远不会变成癌症，这里的“命中”可能会导致更多人过度治疗那些如果未被发现就不会引起问题的癌症，这仍然是前列腺癌和乳腺癌的一个问题。

“If you see a cancer, then you’ve probably got to act on it,” says Hackshaw. “It might be a really good thing if MCED tests preferentially pick up cancers destined to be fatal.”.

“如果你看到癌症，那么你可能必须采取行动，”哈克肖说。“如果MCED测试能够优先发现注定致命的癌症，那可能是一件非常好的事情。”

Some cancers become near impossible to stop as they spread, but not all do — and therapy options continue to emerge for advanced disease. Nabavizadeh says that in his experience, “there’s a lot of stage 3 cancers that we can actually have pretty favourable outcomes for, and identifying that stage 3 cancer is not a loss”.

一些癌症在扩散时变得几乎无法阻止，但并非所有癌症都是如此——针对晚期疾病的治疗选择也在不断涌现。纳巴维扎德表示，在他的经验中，“很多三期癌症实际上我们可以取得相当好的治疗效果，因此发现三期癌症并不意味着失去了希望”。

Thus, even an MCED that falls short on the timeliness dimension could still yield substantial clinical benefit..

因此，即使一个MCED在及时性方面有所欠缺，仍然可能带来显著的临床效益。

Despite the promising diagnostic performance of current MCEDs, oncologists are awaiting proof that these systems actually improve patient outcomes. Beer, Papadopoulos and their colleagues have followed up on people four to five years after the conclusion of DETECT-A, with encouraging results

尽管当前的MCED具有令人鼓舞的诊断性能，但肿瘤学家仍在等待这些系统确实能改善患者预后的证据。比尔、帕帕多普洛斯及其同事在DETECT-A研究结束后的四到五年内对参与者进行了随访，结果令人鼓舞。

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. “The ones that had stage 1 and 2 cancer, and half of the ones that had stage 3, they are still alive,” says Papadopoulos. But this is not proof that MCEDs save lives that would otherwise be lost.

“那些处于癌症第一和第二阶段的患者，以及一半处于第三阶段的患者，他们仍然活着，”帕帕多普洛斯说。但这并不能证明MCEDs拯救了那些本会失去的生命。

The gold standard for assessing efficacy is the randomized controlled clinical trial. Only one such MCED trial is currently under way — a Grail-sponsored trial of Galleri in the UK National Health Service (NHS), which began in 2021 and is expected to report results in 2026.

评估疗效的金标准是随机对照临床试验。目前只有一项这样的MCED试验正在进行中——即Grail公司在英国国家医疗服务体系（NHS）中赞助的Galleri试验，该试验于2021年开始，预计将在2026年报告结果。

But there is considerable debate around how best to measure the benefits delivered by MCED screening. “We have a lot of confidence in cancer-specific mortality,” says Lori Minasian, deputy director of the Division of Cancer Prevention at the US National Cancer Institute (NCI). “If you die of cancer, it’s a pretty objective end point.”.

但是，围绕如何最好地衡量MCED筛查带来的益处，存在相当多的争论。美国国家癌症研究所（NCI）癌症预防部门副主任洛里·米纳西安表示：“我们对癌症特定死亡率有很大信心。如果你死于癌症，这是一个相当客观的终点。”

Still, such end points can make for long, costly studies. Klein cites an NCI trial to study the value of screening for prostate, lung, colon and ovarian cancer, which tracked nearly 155,000 participants between 1993 and 2006. “That cost upwards of US$450 million and it took 20 years for the results to be reported,” Klein says.

尽管如此，这样的终点确实会导致研究周期长且成本高昂。克莱因提到了一项由美国国家癌症研究所（NCI）进行的试验，该试验研究了前列腺癌、肺癌、结肠癌和卵巢癌筛查的价值，在1993年至2006年间跟踪了近15.5万名参与者。克莱因说：“这项研究花费超过4.5亿美元，结果用了20年才公布。”

“I’m not willing to wait, as a professional, for another 10–15 years to have a mortality end point to figure out if this new technology will have a beneficial effect.”.

“作为一名专业人士，我不愿意再等10到15年，等到有死亡终点数据时才确定这种新技术是否会产生有益的效果。”

And so the hunt is on for alternative end points that capture mortality benefit. For the NHS-Galleri trial, the main measure of outcomes is how many advanced cancers are diagnosed among individuals who receive the MCED versus those who do not. This approach is predicated on the idea that early detection will help to prevent the emergence of late-stage cancers, and thus will result in fewer cancers that ultimately prove fatal..

因此，寻找能够体现死亡率益处的替代终点指标的任务已经开始。对于NHS-Galleri试验而言，其主要结局指标是接受MCED检测的人群与未接受检测的人群中诊断出晚期癌症的数量。这种方法基于一个理念，即早期发现将有助于防止晚期癌症的发生，从而减少最终致命的癌症数量。

A 2024 study by Robbins and her colleagues reveals a more complicated story, however. For some cancers, such as of the lung and ovary, early detection seemed to reduce the number of deaths, but this relationship was weak for colorectal and prostate cancer

然而，罗宾斯和她的同事在2024年的一项研究揭示了一个更复杂的情况。对于某些癌症，如肺癌和卵巢癌，早期发现似乎可以减少死亡人数，但这种关系在结直肠癌和前列腺癌中并不明显。

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. “It’s just a big mix of stuff that is all different,” she says, and the extent of this heterogeneity will only grow as the number of cancers being screened for increases.

“这只是一大堆各不相同的东西的混合，”她说，随着筛查的癌症种类增加，这种异质性的程度只会越来越大。

Putting early detection to the test

将早期检测付诸测试

Efforts are under way to bring further clarity to the field. The MCED Consortium has brought together leading figures from academia, industry, government and health care to develop best practices for development, testing and deployment of these systems. And in 2024, the NCI launched the Cancer Screening Research Network, which is preparing to launch its first clinical trial of MCEDs..

各方正在努力为这一领域带来更多 clarity。MCED 联盟汇集了来自学术界、工业界、政府和医疗保健领域的领军人物，以制定这些系统的开发、测试和部署的最佳实践。2024 年，NCI 启动了癌症筛查研究网络，该网络正准备启动其首个 MCED 临床试验。

This trial, known as Vanguard, will evaluate at least two commercially developed MCEDs, and aims to identify sound strategies for recruiting participants, evaluating test performance and developing guidelines for clinical care to accompany screening. “The first question on the docket is, is it feasible?” says Minasian.

这项被称为“先锋”的试验将评估至少两种商业开发的MCED，并旨在确定招募参与者、评估测试性能以及制定伴随筛查的临床护理指南的合理策略。米纳西安说：“首要问题在于，这是否可行？”

But other challenges loom..

但是其他挑战迫在眉睫。

A blood sample is pipetted for analysis.

用移液管吸取血样进行分析。

Credit: Andrew Brookes/ Getty Images

图片来源：Andrew Brookes/ Getty Images

For example, there is the issue of how to proceed after a positive result. Some MCED tests, such as Cancerguard, cannot reveal the tissue source of a tumour signal in the blood, and require follow-up with whole-body imaging. By contrast, Galleri’s algorithms can reveal the location of a suspected tumour with striking accuracy, entirely on the basis of cfDNA profiling.

例如，有一个问题是如何在阳性结果后进行。一些MCED测试，如Cancerguard，无法揭示血液中肿瘤信号的组织来源，需要通过全身成像进行后续检查。相比之下，Galleri的算法可以仅基于cfDNA分析，以惊人的准确性揭示疑似肿瘤的位置。

But these results are presented as probabilities — and the highest-ranked tissue source might not always reflect a tumour’s true location..

但是，这些结果是以概率形式呈现的——并且排名最高的组织来源可能并不总是反映肿瘤的真实位置。

Different tissues require different follow-up procedures, and Etzioni is concerned that confirmation could require substantial effort. “You need a statistician and a radiologist sitting together to figure out how to strategize it,” she says. This could become a substantial obstacle to widespread deployment of MCED screening, and might require reorganization in the health-care system.

不同组织需要不同的后续程序，而 Etzioni 担心确认工作可能需要耗费大量精力。“你需要一个统计学家和一个放射科医生坐在一起，研究如何制定策略，”她说道。这可能会成为 MCED 筛查广泛推广的重大障碍，并且可能需要对医疗系统进行重组。

Nabavizadeh advocates creating regional centres of MCED excellence, which would be staffed with specialists who can assist those facilities that lack the expertise to properly validate MCED results..

纳巴维扎德主张建立区域性的MCED卓越中心，这些中心将配备能够帮助那些缺乏适当验证MCED结果的专业知识的设施的专家。

Nevertheless, the clinical community as a whole will need to be educated about how to use MCEDs effectively and what their obligations are in following up. “There are no guidelines on when to stop, how much to do, and if I stop too soon, will I be sued?” says Minasian.

然而，整个临床界需要接受关于如何有效使用MCED以及他们在后续工作中应承担的责任的教育。米纳西安说：“目前尚无关于何时停止、做多少以及如果我过早停止，我是否会被告上法庭的指导方针？”

Patients will also need to understand the realities of these tests, and that a seemingly clean bill of health from a well-validated MCED does not mean they can skip the colonoscopies or mammograms. “MCED testing is intended to be used in addition to ‘standard of care’ screening, not to replace it,” says Klein..

患者还需要了解这些测试的实际情况，要知道从一个经过充分验证的MCED获得的看似干净的健康报告并不意味着他们可以跳过结肠镜检查或乳腺X光检查。“MCED测试旨在作为‘标准护理’筛查的补充，而不是取代它，”克莱因说。

Both Exact Sciences and Grail are conducting multiyear prospective studies to evaluate the benefits and impact of MCED screening, and how people respond in the aftermath of negative or positive test results. Exact Sciences’ Falcon study, launched last year, will track 25,000 participants for 5 years.

Exact Sciences 和 Grail 都在进行多年前瞻性研究，以评估 MCED 筛查的益处和影响，以及人们在检测结果为阴性或阳性后的反应。Exact Sciences 去年启动的 Falcon 研究将在未来 5 年内跟踪 25,000 名参与者。

“We’re going to be looking at how patients feel about their experience,” says Beer. A prime concern, he adds, will be “making sure that people don’t use a negative blood test as a reason to skip standard-of-care screening”..

“我们将关注患者对他们的体验有何感受，”比尔说。他补充说，一个主要关注点将是“确保人们不会因为血液检测呈阴性而跳过标准的护理筛查”。

In the United States, there are pathways that allow the public to access MCED testing even without formal regulatory approval from the US Food and Drug Administration (FDA). Grail’s Galleri test has already been prescribed to numerous US patients, and Klein says that the resulting data — from 290,000 tests so far — offer valuable insight into Galleri’s real-world performance.

在美国，即使没有获得美国食品药品监督管理局（FDA）的正式批准，也存在允许公众获取MCED检测的途径。Grail公司的Galleri测试已经被开给了许多美国患者，Klein表示，迄今为止从29万次测试中获得的数据为Galleri在现实世界中的表现提供了宝贵的见解。

“It’s naysayers who say, ‘well, we can’t do anything until the FDA approves it’,” says Klein. The FDA is looking into tightening rules around its oversight of such ‘laboratory-developed tests’ (LDTs), but with a new presidential administration now in place, the future of LDT regulation is an open question..

“那些唱反调的人说，‘嗯，我们什么也做不了，直到FDA批准它’，”克莱因说。FDA正在考虑加强对这类“实验室开发测试”（LDTs）的监管规则，但随着新的总统政府上台，LDT监管的未来是一个未知数。

Minasian is among those who are concerned about moving too quickly to market with a new category of tests — especially if other test developers follow Grail’s lead, presenting clinicians and patients with a confusing abundance of options. “What we really don’t know is how best to use it — I’m not sure that these are optimal for everybody who’s at low risk,” she says.

米纳西安是那些担心过快将新类别的测试推向市场的人之一，尤其是如果其他测试开发者效仿格雷尔的做法，这将给临床医生和患者带来令人困惑的过多选择。“我们真正不知道的是如何最好地使用它——我不确定这些测试是否对所有低风险人群都是最佳选择，”她说。

Still, she adds, “they’re good enough that we want to study them so that we can figure out how to use them the right way, so that everybody benefits.”.

不过，她补充说：“它们已经足够好，我们想要研究它们，这样我们就能找出如何正确使用它们，让每个人都受益。”